Article: Vioxx: How patients and doctors were deceived

This is a draft of an article published in the Times in February 2005 [Unable to find it online]

It was written shortly after the anti-inflammatory drug Vioxx had been withdrawn because it raised the risk of heart disease. After its withdrawal it became clear that the company had gone to extraordinary lengths to conceal the problems, including distorting results and threatening researchers who questioned the drugs’s safety.

Actively harassing

By now most of seven million people in the UK who suffer from arthritis will know that Vioxx, a new type of widely prescribed anti-inflammatory drug, has been withdrawn because it doubled the risk of a heart attack. But until this week it wasn’t clear why. Australian scientists have just reported that Vioxx and other drugs of this type – cox-2 inhibitors – significantly raise blood pressure, which is a major risk factor for heart disease.

Meanwhile another team at the big American centre, Johns Hopkins, has just found that these drugs also cut back on one of chemicals in the brain that can protect neurons after a stroke. These are just the latest in an extraordinary string of revelations over the past five months about the dangers of the cox-2 drugs, which have left thousands worried they may have been damaged. The good news is that a variety of other products can bring relief.

The crisis began four months ago on September 30th when Vioxx, prescribed to 400,000 people in the UK and taken by 80 million world-wide was suddenly withdrawn by the manufacturers Merck. At first Merck was commended for its prompt action, but evidence rapidly emerged which suggested that not only had the company known about the side-effect for years but had also actively harassed – and in one case sued – independent researchers who raised the issue of possible dangers. (see below))

Unacceptable risks

In December top UK medical journal the Lancet published an angry editorial which declared that “the unacceptable cardiovascular risks of Vioxx were evident as early as 2000,” and condemned the “astonishing failures” in picking up these problems after the drug was launched. The article estimated that Vioxx had caused an extra 27,000 heart attacks and deaths.

By the end of January, however that figure had risen dramatically. Another Lancet study put the number of “excess cases of serious coronary heart disease” from Vioxx at between 88,000 and 140,000. “People taking Vioxx had a 34% higher chance of coronary heart disease than those taking other NSAIDS,” it concluded.

It is findings like these that have led lawyers in both this country and America to mount compensation cases against Merck. “I’ve had two heart attacks in the last four months,” says 57-year-old Robert Green whose case is being handled by Leigh Day and Co in London. He had been taking Vioxx for four years during which time his blood pressure rose and he began to have chest pains. “I have no history of heart problems in my family,” he says. “No one warned me about any dangers of heart attacks. I’m not taking anything for my arthritis now and getting out of bed in the morning can be murder.”

Vioxx is one of a class of drugs known as cox-2 inhibitors which were developed to overcome the gastrointestinal damage that pain-killers such aspirin and ibuprofen can cause when used to treat long term. These drugs, known as NSAIDS (non steroidal anti inflammatories), cause about 12,000 hospital admissions a year in the UK and 2,600 deaths – equivalent to the mortality rate from cervical cancer and melanoma combined.

Dangers of NSAIDS

Later this month the Federal Drug Administration will be considering whether to withdraw all cox-2 inhibitors. Already leading American cardiologists have called for two of them – Celebrex and Bextra to be stamped with a “black box” warning. Celebrex, used by 600,000 people in the UK, has also been found to double or triple the risk of heart attack.

If that happens, going back to NSAIDS isn’t really an option long term. A British Medical Journal (BMJ) report in December found they were little better than a placebo at handling the pain of osteoarthritis and, because of the side effects, recommended they should not be taken for more than a week. Since then the picture for arthritis sufferers relying on drugs has become even bleaker.

One small study, using new scanning technology has found that NSAIDS may damage more than the stomach. Seventy percent of patients who had been on NSAIDS for three months had visible damage to their small intestine. What’s more, a majority of the people on cox-2 inhibitors were gaining no benefit from them.

Developed specifically not to damage to the stomach, there was never any evidence they were any more effective at reducing pain and inflammation than NSAIDS. However 70% of the cox-2 prescriptions were given to people without a high risk of stomach damage.

What else can you do

Faced with the choice of bleeding guts or heart attacks some arthritis experts have recommended that patients chose their pain relief on the basis of their “individual risk for heart disease or stomach problems.”

However there is another way. In recent months there has been a virtual glut of positive results for a variety of CAM (complementary and alternative) treatments. The Christmas edition of the BMJ, for instance, carried reports that two long-term favourites – magnetic bracelets and acupuncture – both performed better than a placebo. In the case of the bracelet, a placebo controlled trial involving 194 patients found that the bracelet decreased pain by about the same amount as Cox2 inhibitors.

Many arthritis sufferers will already have tried omega 3 oil and glucosamine, both of which have trials in their favour, although a short 3-month study last autumn found glucosamine to be no better than a placebo. Less familiar, but also backed by evidence from small scale trials, are such remedies as ginger, vitamin B3 and an enzyme that comes from pineapple called Bromelain – in a recent study 59% of those who used it reported an improvement.

Other more exotic options include “Blue Ease cream” which contains Emu Oil – long used by the Aborigines to relieve muscle and joint pain. The makers claim its anti-inflammatory relief is equal to ibuprofen. Also Devil’s Claw (Harpagophytum procumbens), a traditional African remedy, has a number of studies showing its effectiveness.

Just last month a study double blind study of Civamide cream – a synthetic version of capsaicin (the hot ingredient in chillies) found a “statistically significant improvement” in pain and movement in 695 patients. Collagen hydrolysate is a form of gelatine that has been found to reduce pain and slow down the rate at which joints wear away. It’s little known in the UK but more widely used in Germany.

“There are very few reliable clinical trials of these complementary approaches,” warns Dr. Madeleine Devey, scientific advisor to the Arthritis Resarch Campaign. “There are other safer drugs that people can use like codeine and paracetamol and many people benefit from learning techniques of pain management. It’s a matter of finding what works for you.”

Mr Roberts, waiting to hear about the heart operation he needs, is hoping desperately he finds that combination soon.

Keeping Quiet

Just how hard Merck fought to keep the link between Vioxx and heart problems under wraps was revealed by the Wall Street Journal in November. Company emails showed that their researchers had been worried about the heart risk as far back as 1996. An internal document intended for the sales team about how to deal with tough questions on Vioxx was labelled “Dodge Ball Vioxx”. Merck also targeted indepdent academics who questioned the drug’s safety. A Spanish pharmacologist was sued in an unsuccessful attempt to force a correction of an article, while a Stanford University researcher was warned that he would be “flamed out” unless he stopped giving “anti-Merck” lectures.

Last month it emerged that the company forced one of its researchers to remove her name from a study involving over 50,000 patients that linked Vioxx with heart attacks. It was published just six months before the drug was withdrawn. Pressure not to publish was also brought to bear on Dr David Graham, who works in the office of drug safety at the FDA. The agency threatened him with dismissal if he prublished the study showing that Vioxx had been linked with between 80,000 and 140,000 excess cases of heart disease in the USA.